环状RNA（circRNA）家族是一组内源性非编码RNA（ncRNA），在炎症、癌症和心血管疾病等多种生理和病理过程中具有关键功能。然而，它们在调节先天免疫反应中的作用仍不清楚。在这里，我们定义了细胞分裂周期 42 (CDC42)-165aa，这是一种由 circRNA circCDC42 编码的蛋白质，在肺炎克雷伯菌 (KP) 感染的肺泡巨噬细胞中过度表达。高水平的CDC42-165aa会诱导Pyrin炎症小体过度激活，加重肺泡巨噬细胞焦亡，而抑制CDC42-165aa则通过抑制Pyrin炎症小体介导的焦亡来减轻KP感染后小鼠的肺损伤。总体而言，这些结果表明 CDC42-165aa 通过抑制 CDC42 GTPase 激活来刺激 Pyrin 炎症小体，并为临床实践中的病原菌感染提供潜在的临床靶标。© 2024。作者。

The circular RNA (circRNA) family is a group of endogenous non-coding RNAs (ncRNAs) that have critical functions in multiple physiological and pathological processes, including inflammation, cancer, and cardiovascular diseases. However, their roles in regulating innate immune responses remain unclear. Here, we define Cell division cycle 42 (CDC42)-165aa, a protein encoded by circRNA circCDC42, which is overexpressed in Klebsiella pneumoniae (KP)-infected alveolar macrophages. High levels of CDC42-165aa induces the hyperactivation of Pyrin inflammasomes and aggravates alveolar macrophage pyroptosis, while the inhibition of CDC42-165aa reduces lung injury in mice after KP infection by inhibiting Pyrin inflammasome-mediated pyroptosis. Overall, these results demonstrate that CDC42-165aa stimulates Pyrin inflammasome by inhibiting CDC42 GTPase activation and provides a potential clinical target for pathogenic bacterial infection in clinical practice.© 2024. The Author(s).